title: IL-10 production from dendritic cells is associated with DC SIGN in human leprosy.
abstract: The defective antigen presenting ability of antigen presenting cells (APCs) modulates host cytokines and co-stimulatory signals that may lead to severity of leprosy. In the present study, we sought to evaluate the phenotypic features of APCs along with whether DC SIGN (DC-specific intercellular adhesion molecule-grabbing nonintegrin) influences IL-10 production while moving from tuberculoid (BT/TT) to lepromatous (BL/LL) pole in leprosy pathogenesis. The study revealed an increased expression of DC SIGN on CD11c⁺ cells from BL/LL patients and an impaired form of CD83 (∼50 kDa). However, the cells after treatment with GM-CSF+IL-4+ManLAM showed an increased expression of similar form of CD83 on DCs. Upon treatment with ManLAM, DCs were found to show increased nuclear presence of NF-κB, thus leading to higher IL-10 production. High IL-10 production from ManLAM treated PBMCs further suggested the role of DC SIGN in subverting the DCs function towards BL/LL pole of leprosy. Anti-DC SIGN treatment resulting in restricted nuclear ingression of NF-κB as well as its acetylation along with enhanced T cell proliferation validated our findings. In conclusion, Mycobacterium leprae component triggers DC SIGN on DCs to induce production of IL-10 by modulating intracellular signalling pathway at the level of transcription factor NF-κB towards BL/LL pole of disease.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Kumar
authors.forename: Raza Ali
authors.initials: RA
authors.lastname: Naqvi
authors.forename: Ajaz A
authors.initials: AA
authors.lastname: Bhat
authors.forename: Richa
authors.initials: R
authors.lastname: Rani
authors.forename: Riyasat
authors.initials: R
authors.lastname: Ali
authors.forename: Abhishek
authors.initials: A
authors.lastname: Agnihotri
authors.forename: Neena
authors.initials: N
authors.lastname: Khanna
authors.forename: D N
authors.initials: DN
authors.lastname: Rao
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000293:Adolescent; D000328:Adult; D019138:Antibodies, Blocking / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D018450:Disease Progression; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D057131:Immune Evasion; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D007918:Leprosy / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009166:Mycobacterium leprae / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D019138:Antibodies, Blocking; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016753:Interleukin-10; D015847:Interleukin-4; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C050016:lipoarabinomannan
keywords: DC SIGN; Leprosy; ManLAM; Mycobacterium leprae; NF-κB; p300